SUMMARY
WP2 uses cutting-edge omics technologies and AI to addresses a critical knowledge gap: the lack of cell-type-specific insights into lung transplant rejection. By analyzing cellular mechanisms using spatial transcriptomics, proteomics, and TCR sequencing, researchers can uncover the complex molecular and immune mechanisms at play during rejection and tissue injury and identify key gene targets for intervention.
WP2 leader is Prof. Holger Heyn, from Omniscope.
Single-cell sequencing reveals gene targets
KU Leuven (DC1) will use single-nucleus and single-cell RNA sequencing to identify precise gene expression changes in different stages of lung injury and rejection. By analyzing 20 lung samples for IRI and 22 for CLAD (fibrotic and bronchiolitis phenotypes), this effort will uncover cell-specific gene targets. These data will feed into AI tools like scMysterYdentifier and GenePrior-v2.0 to prioritize therapeutic candidates for further validation.
Immune profiling through TCR sequencing
T cell receptor (TCR) sequencing, led by DC6 (OMNI), enables monitoring of immune responses pre- and post-transplant. TCR profiling identifies key clones responsible for graft rejection, potentially pointing to therapeutic targets. Combined with scRNA-seq, this data will be used to build predictive models for primary graft dysfunction (PGD) and chronic rejection, helping personalize patient monitoring and intervention strategies.
High-resolution spatial analysis of lung tissue markers
Lunds Universitet (DC5) and Miltenyi Biotec (DC7) will use MACSima™ and RNASky™ platforms for deep tissue profiling, capturing both RNA and protein markers in lung tissue. These tools will provide spatially-resolved insights into how gene therapy, such as viral vector-mediated immunomodulation, alters immune environments. Combined with laser capture microdissection and mass spectrometry, this work supports the development of more targeted and effective transplant interventions.
